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Biomedical subjects

P Newman

Publications and source records attributed to P Newman.

At least 19 recordsLinked to original sources

Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakarocytes.

Immunoblot analyses indicate that the platelet is a reservoir of several Alzheimer amyloid precursor protein (APP) isoforms, including C-terminal reactive species which could potentially serve as the precursor of the amyloid beta protein (AB*) in Alzheimer's disease (AD). Since platelets are known to sequester several plasma proteins from the blood, we employed the polymerase chain reaction (PCR) to amplify reverse transcribed mRNA and detect the 3 major APP transcripts (APP695,751,770) in platelets and the Dami megakaryocyte cell line. PCR amplification of glycoprotein IIb and HLA-DR mRNA was used to demonstrate that APP transcripts were derived from cells of megakaryocytic lineage, and the results were compared with those obtained from peripheral blood mononuclear cells, human umbilical vein endothelial cells, B lymphocyte and astrocytoma cell lines. The identity of PCR products was confirmed by hybridization with APP specific oligonucleotide probes, and sequencing of amplified segments.

Amyloid beta-Protein Precursor

Polyisoprenylation of the CAAX motif--an in vitro protein synthesis study.

A number of proteins, including most nuclear lamins, certain fungal mating pheromones, G-protein gamma-subunits and ras proteins, contain a C-terminal cysteine-aliphatic-aliphatic-undefined amino acid (CAAX) motif which is thought to be a roughly defined consensus sequence capable of directing a series of posttranslational events, beginning with the addition of a polyisoprene moiety to the cysteine. So far such a motif has been found in every protein known to have this type of modification. We have utilized the rabbit reticulocyte lysate translation system, which is capable of carrying out the polyisoprene modification in vitro, to investigate features of the C-terminal motif which affect its suitability as a substrate. We demonstrate that a cysteine is only isoprenylated when situated at position -4 from the C-terminus. We further show that the presence of a glycine at position -3 or a terminal aromatic residue, features typical of some G-protein alpha subunits, cause a reduction and abolition respectively of isoprenylation.

Amino Acid Sequence

Squamous carcinoma in the liver.

Squamous carcinoma of the liver has only rarely been reported. We present a case which highlights not only the difficulties in diagnosis but also how it can closely mimic sclerosing cholangitis.

Aged

Influence of cytochalasin D-induced changes in cell shape on proteoglycan synthesis by cultured articular chondrocytes.

There is growing evidence that cell shape regulates both proliferation and differentiated gene expression in a variety of cell types. We have explored the relationship between the morphology of articular chondrocytes in culture and the amount and type of proteoglycan they synthesize, using cytochalasin D to induce reversible cell rounding. When chondrocytes were prevented from spreading or when spread cells were induced to round up, 35SO4 incorporation into proteoglycan was stimulated. Incorporation into the cell layer was stimulated more than into the medium. When the cells were allowed to respread by removing cytochalasin D, proteoglycan synthesis returned to control levels. Cytochalasin D-induced stimulation of 35SO4 incorporation reflected an increase in core protein synthesis rather than lengthening of glycosaminoglycan chains, because [3H]serine incorporation into core protein was also stimulated. The observed stimulation of proteoglycan synthesis was not due to an overall stimulation of protein synthesis, to inhibition of DNA synthesis, or to accumulation of cells in one phase of the cell cycle. Cytochalasin D-treatment of cells in suspension caused no further stimulation of 35SO4 incorporation, suggesting that the observed effects were due to cell rounding rather than exposure to cytochalasin D per se; nevertheless, we cannot completely rule out other, nonspecific, effects of the drug. Fibroblasts and chondrocytes that had been passaged to stimulate dedifferentiation did not incorporate more 35SO4 when treated with cytochalasin D, suggesting that increased proteoglycan synthesis in response to rounding may itself be a differentiated property of chondrocytes.

Animals

Chondrosarcoma of the epiglottis.

Malignant cartilaginous tumours of the larynx are very rare, and usually arise from the cricoid cartilage. We report the first documented case of a chondrosarcoma of the epiglottis. The diagnosis, histology and treatment of these tumours are discussed.

Chondrosarcoma

Phenotypic properties, interleukin 2 production, and developmental origin of a "mature" subpopulation of Lyt-2- L3T4- mouse thymocytes.

Two-color flow microfluorometry using monoclonal antibodies to cell surface determinants has shown that a subpopulation of mouse Lyt-2- L3T4- thymocytes, comprising 18% of Lyt-2- L3T4- cells in adult C57BL/6 mice, appears in the thymus late during fetal development. These Lyt-2- L3T4- cells are characterized by lack of expression of determinants recognized by monoclonal antibody J11d, a phenotype characteristic of more "mature" functional T cells. This J11d- subpopulation of Lyt-2- L3T4- thymocytes has now been shown to produce significant quantities of interleukin 2 following mitogen stimulation and to express T-cell receptor molecules recognized by monoclonal antibodies KJ-16 and F23.1. Furthermore, culturing of fetal thymus lobes has shown that precursors of this subpopulation of Lyt-2- L3T4- thymocytes are already present in thymus at 14 days of embryonic development and are thus derived from an intrathymic precursor cell. So, within the mouse thymus, phenotypic changes and acquisition of mature T-cell characteristics occur within a subpopulation of cells originally thought of as exclusively "immature."

Age Factors

Adverse effect of smoking on the hyperaemic response in diabetic patients and control subjects.

In order to determine whether smoking had an adverse effect on the hyperaemic response, as measured by transcutaneous oximetry, matched groups of insulin-dependent diabetic smokers and non-smokers were compared both with each other and with similar matched groups of non-diabetic control subjects. The hyperaemic response was also measured immediately, 1 hour and 24 hours after smoking a cigarette in five control subjects who smoked. The hyperaemic response was significantly lower in the diabetic smokers compared with the diabetic non-smokers (p = 0.008) and in the control smokers compared with the control non-smokers (p = 0.011). No other significant differences were found. In the five subjects studied at intervals after smoking the responses were variable and inconsistent. Smoking modifies the hyperaemic response and this must be taken into account in any investigation using such measurements.

Adult

Toxicity manifestations following intravenous Corynebacterium parvum administration to patients with ovarian and cervical carcinoma.

Manifestations of clinical toxicity were evaluated following 341 courses of intravenous Corynebacterium parvum adjuvant immunotherapy in patients with ovarian and cervical carcinoma. Most patients exhibited symptoms of minor toxicity, which decreased in intensity as subsequent courses of therapy were administered. Temperature elevations to 38.5 degrees C. were the most objectively measured signs of toxicity but temperature elevations greater than 38.5 degrees C. occurred following only 20.5 per cent of the infusions. Blood pressure alterations were not a serious problem and no serious central nervous system or renal toxicity was noted. The minor side effects should not preclude the use of C. parvum as an immunopotentiating agent if it is shown to be beneficial in the treatment of human malignant disease.

Blood Pressure

Assessment of rheumatoid inflammation in the knee joint. A reappraisal.

Subjective pain score, clinical assessment, 99m technetium joint uptake, infrared thermography, and thermistor skin temperature measurements were evaluated and compared in patients with rheumatoid knee treated with intra-articular hydrocortisone. In 11 patients with definite and classical rheumatoid arthritis, 10 of whom had unilateral knee involvement, the affected knee joints were assessed by the above techniques before and at intervals after treatment of up to 14 days. The anti-inflammatory property of the steroid therapy was shown by all the assessment parameters, values having decreased significantly from the pretreatment values. However, the only parameter still showing a statistically significant decrease on the 14th post-treatment day was 99mTc joint uptake. Correlations were obtained between the two clinical measurements assessed by a physician i.e. pain score and index of joint inflammation. Both of these also correlated with the 99mTc joint uptake but not with skin temperature measurements. Using the clinical assessments as a yardstick, 99mTc joint uptake seemed to provide a useful index of changes in disease activity in the group as a whole. However, skin temperature measurements by infrared thermography and by the thermistor were of considerably less value.

Arthritis, Rheumatoid

Tuberculous brain abscess.

Brain abscess is probably the least common manifestation of tuberculous infection of the central nervous system. Some authors have made a rigid distinction between tuberculous brain abscess and variants of cerebral tuberculoma. Such a distinction is not supported by our own case of tuberculous brain abscess, or by review of similar, recently reported cases.

Brain Abscess